US4399225A - Stop-flow analysis - Google Patents

Stop-flow analysis Download PDF

Info

Publication number
US4399225A
US4399225A US06296256 US29625681A US4399225A US 4399225 A US4399225 A US 4399225A US 06296256 US06296256 US 06296256 US 29625681 A US29625681 A US 29625681A US 4399225 A US4399225 A US 4399225A
Authority
US
Grant status
Grant
Patent type
Prior art keywords
sample
concentration
reaction
carrier stream
selected
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
US06296256
Inventor
Elo H. Hansen
Jaromir Ruzicka
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Bifok AB
Original Assignee
Bifok AB
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Grant date

Links

Images

Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/08Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
    • G01N35/085Flow Injection Analysis
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/54Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving glucose or galactose
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using infra-red, visible or ultra-violet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/27Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands using photo-electric detection ; circuits for computing concentration
    • G01N21/272Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands using photo-electric detection ; circuits for computing concentration for following a reaction, e.g. for determining photometrically a reaction rate (photometric cinetic analysis)
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10TTECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00Chemistry: analytical and immunological testing
    • Y10T436/11Automated chemical analysis
    • Y10T436/117497Automated chemical analysis with a continuously flowing sample or carrier stream
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10TTECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00Chemistry: analytical and immunological testing
    • Y10T436/11Automated chemical analysis
    • Y10T436/117497Automated chemical analysis with a continuously flowing sample or carrier stream
    • Y10T436/118339Automated chemical analysis with a continuously flowing sample or carrier stream with formation of a segmented stream

Abstract

A continuous method of quantitatively determining slowly reacting compounds with the use of a single measuring cell, the sample being injected into a continuously flowing carrier solution which is already provided with, or simultaneously with the sample is provided with reagent to form a sample zone in the form of a reproduceable gradient. Said sample zone is led into a measuring cell whereupon the flow is stopped by means of shunting the carrier flow, by stopping the pump, or by means of a valve. The reaction is allowed to take place in the measuring cell while a magnitude, characteristic for the reaction, is registered. The reaction speed can be detected from the incline of the obtained response curve and the amount of the sought-after compounds is calculated. By means of setting the stop at a certain point in the concentration gradient curve and always selecting said point at the same time distance from the peak of the gradient curve during flow, a total reproduceability of the analysis is ensured.

Description

This is a continuation of application Ser. No. 048,002 filed June 13, 1979, now abandoned.

The present invention is a further development of our original flow injection analysis, that is, analysis with injection of a sample in a continuously flowing continuous carrier solution.

Our continuous analysis method is protected by a number of patents and patent applications in different countries and the principles are described in detail in our previous patent, U.S. Pat. No. 4,022,575.

Flow injection analysis is based on the analysis system being designed so that a reproduceable gradient of the sample is formed in a reagent flow and that measurements of the formed gradient curve, for example spectrophotometric, potentiometric etc. measurements are carried out.

However, in kinetic reactions one can obtain both better selectivity and sensitivity in a sample by studying the reaction speed. Such speed measurements are necessary when enzyme activity and catalytic activity are measured. The basis for our present invention is measurement of the chemical reaction speed. In order to determine the linear part of the reaction response curve so that its derivate or angle, that is, the reaction speed, can be measured with certainty, it is desirable to obtain as many measuring points as possible for each individual analysis. That is difficult to achieve in current continuous flow analysis as the only possible method of analysis has been to place several measuring cells or detectors in succession in the same flow. This is very clumsy and discrete analyses, especially in their most advanced form with centrifugal analysers, have thus a key position for enzyme analyses by means of the signal being able to be detected continuously by these instruments from the moment the reagent and the sample are mixed together.

The purpose of the present invention is to carry out analysis in slow reactions in a simpler and simultaneously considerably more thorough manner.

In the so-called stop-flow method according to the present invention, a single measuring instrument such as a spectrophotometer, a potentiometer etc. is used for detecting the desired magnitude and stops the flow through the measuring cell at a suitable point in time. Thus, the flow can be stopped in various ways; for example, the carrier solution pump can be stopped or the flow can be shut off with a valve arranged before the measuring cell. However, one can also allow the flow to continue without interruption by means of leading it through a shunt conduit past the measuring cell.

By means of its construction, the continuous flow injection analysis allows different means of carrying out the analysis itself. This is something entirely unique for the process.

Firstly, in normal kinetic measurements, two reagent solutions can be led through a mixing chamber so as to obtain a total and immediate mixture of the reaction solutions which each other so that the chemical reaction in the immediately homogenised mixture can begin to be detected within a few milliseconds.

However, such a quick mixture is not desirable in many cases, for example in enzymatic analysis, where a first retarded phase of the magnitude of several seconds often arises. In flow injection analysis, the sample zone, during passage through a tube or coil, is first subjected to a controlled dispersion in the carrier solution which was previously mixed with the reagent (the enzyme solution) and then stops the flow in the measuring cell and detects the chemical reaction continuously on the basis of the reproducable sample gradient formed in the flow. In many cases, it provides better results to start from the concentration gradients formed during the slow dispersion of the sample zone instead of restricting oneself to measurements of a homogenous solution obtained by means of quick and effective mixture.

The invention shall be described in more detail below in connection with an embodiment and the accompanying drawings, in which

FIG. 1 is an analysis apparatus according to the present invention,

FIGS. 2 and 3 are principle reaction curves in the apparatus,

FIG. 4 is a calibration curve for practical use, and

FIG. 5 is another analysis apparatus according to the present invention.

The specific reaction between glucose dehydrogenase and β-D glucose is used for the kinetic determination of glucose for investigation and verification of the stop-flow injection principle.

A commerical system glucose enzyme from Merck was used, whereby the co-enzyme nicotinamide-adenin-dinucleotide, NADH, serves as a chromophoric indicator which can be spectrophotometrically measured at 340 nm. Analytical Chimica Acta, 89, (1977), pp. 241-244 presents the background chemistry and reagent compositions and tests with kenetic measurements in one and two points.

The apparatus arrangement in the present tests is shown in FIG. 1. The enzyme and carrier solution is continuously led through a conduit 1 in a continuous flow via a peristaltic pump 2 in an amount of 2.5 ml/min. to a thermostat 3 set at 37° C., where the carrier flow is thermostated in a first coil 4 having a diameter of 0.75 mm and a length of 450 mm in the present case. After said first coil 4, the sample is led to a sample adding apparatus 5, for example of the kind described in detail in our U.S. Pat. No. 4,177,677 issued Dec. 11, 1979, and the mixture of carrier solution, enzyme and sample is allowed to continue through a second coil 6 having a diameter of 0.50 mm and a length of 300 mm to a spectrophotometer 7, where measuring takes place at 340 nm. The solution is led from the spectrophotometer 7 out through the tube 8. As is the case with the coil 4, the coil 6 and the spectrophotometer 7 are situated inside the thermostate 3 which is set at 37° C.

The first test series was made so that the concentration of glucose in the injected sample, 30 microliters, was increased from 1 to 20 millimoles/liter and the sample zone was stopped in the measuring cell as soon as the registered curve reached its maximum. When the flow was interrupted for 9 seconds, a measuring cycle consisting of three parts was obtained; (a) sample injection, dispersion and transportation into the detector, 4.5 seconds, (b) the measuring period with the stopped flow, 9 seconds, (c) the washing period, 10 seconds, after which the next sample was immediately injected. FIG. 2 shows how the sample is added at 0 time, the flow is stopped at 4.5 seconds and started again at 13.5 seconds. This method allows a multi-point, kinetic determination with a speed of 150 samples per hour.

Another aspect of the kinetic analysis according to the invention is shown in FIG. 3 where, in a second test series, the concentration in the injected samples was held constant at 15 mM, but the flow was stopped at different points in time. The dashed curves show how, at a stop, deviation from the solid line measuring curve obtained during continuous flow takes place. By means of the presence of the concentration gradient profiles, different reaction stages between the sample and reagent solution were available for measurement. Thus, the registered response curves obtain different angles and, thus, it is important to always carry out the kinetic measurement in the same section of the sample zone, as was done in the first experiment series. For this type of analysis, the top detector provides a possibility of reproduceably selecting any section of the dispersed sample zone after the maximum peak. Said further flexibility for selection of the ratio sample/reagent provides many interesting aspects for analysis of enzymes.

On the basis of the above-mentioned principle, a number of analyses of glucose have been carried out. A calibration curve was set up on the basis of an arbitrarily selected curve in FIG. 3 with a number of different standard samples. In the calibration curve, the slope is disclosed in mm/4 seconds as a function of mMole glucose. As described above, the measurements were made at a thermostating to 37° C. and with NADH as indicator and measuring at 340 nm.

Analyses were then made of the same samples using a common autoanalyser according to D. Banauch, W. Brummer, W. Ebeling, H. Metz, H. Rindfrey, H. Lang, K. Leybold and W. Rick, Z. Klin; Chem.Klin.Biochem.,13 (1975) 101, and with our novel method using the calibration curve in FIG. 4.

The following results in mMole glucose/l were obtained:

______________________________________Autoanalyser   Stop-flow______________________________________5.3            5.68.6            9.54.7            4.96.5            6.4______________________________________

As can be seen in the table, the use of the present invention provides results corresponding well with previous methods, but in a much quicker and simpler manner.

As the enzyme or substrate solution is often very expensive, it is economically advantageous not always to be forced to pump it through the analysis apparatus as it only needs to be present in that part of the flow containing the sample zone. This demand is met by an apparatus of the kind shown in FIG. 5, where two exactly synchronized injection valves are used, one having 10 microliters volume for sample injection and the other 9 having a 30 microliter volume for injection of the enzyme reagent. The carrier flow consisted of distilled water. The conduits 11 and 12 were carefully adapted, each having a length of 10 mm and an inner diameter of 0.5 mm, in order to provide an exact synchronisation of the sample zone and the reagent zone at meeting point 13. The other reference numerals in FIG. 5 have the same meanings as corresponding reference numerals in FIG. 1.

As in FIG. 1, FIG. 5 shows thermostating of the flows between the peristaltic pump 2 and the sample addition valves. In the latter embodiment according to FIG. 5, however, said thermostating prior to addition can be avoided as no reaction takes place until after the meeting point 13, and the conduits 11 and 12 suffice to ensure a temperature equilibrium before the reaction takes place after the meeting point 13.

The determination of glucose with the use of glucose hydrogenase as enzyme, based on the previously disclosed chemistry, provided results identical to results obtained when the carrier flow always consisted of glucose hydrogenase in the phosphate buffer, FIGS. 1-4. Even if the enzyme reagent solution must be more concentrated in reaction injection than in the continuously flowing reaction solution when the reaction zone is dispersed, a considerable savings of the enzyme reagent is obtained. When the pumping time in the first test was a total of 15 seconds and the pumping speed was 2.5 ml/minute, corresponding to 0.6 ml, 1.4 kU/l, only 0.03 ml enzyme was consumed per analysis in the second test, 7.04 kU/l glucose hydrogenase, that is, enzyme production was reduced to a fourth. By means of water being used as carrier solution, washing of the apparati between different analyses is avoided. In any case, washing is reduced to a minimum.

Claims (15)

What we claim is:
1. A method for determining the reaction speed of a sample at selected sample concentrations within a sample mixture slug comprising the steps of:
introducing a sample into a flowing carrier stream to form a sample mixture slug having a forward head portion, a rearward tail portion and a central portion, said sample dispersing within said sample mixture slug to form reproduceable concentration gradients in said head and tail portions in which the concentration of said sample varies;
flowing said carrier stream and sample mixture slug through a measuring cell without removing the head portion or tail portion from said sample mixture slug;
stopping the flow of said carrier stream in response to a selected concentration of sample within one of said concentration gradients as said sample mixture slug passes through said measuring cell; and
measuring the reaction of said sample at said selected concentration for a period of time whereby said reaction speed of said sample at said selected sample concentration may be determined.
2. A method according to claim 1 wherein one or more reagents are introduced into said carrier stream to form a reagent carrier stream having reagent uniformly dispersed therein for reaction with sample.
3. A method according to claim 2 wherein said selected sample concentration is determined by measuring a reaction product of said sample and said reagent.
4. A method according to claim 3 wherein samples are sequentially introduced into said flowing carrier stream.
5. A method according to claim 3 wherein said sample concentrations are selected by varying the time period between introduction of said sample into said carrier stream and stopping said carrier stream flow.
6. A method according to claim 2 wherein said reagent is introduced into said carrier stream after said sample is introduced therein.
7. A method according to claim 2 or 6 where said reagent is introduced noncontinuously into said carrier stream as a discrete reagent slug in such a manner to provide mixing of said sample mixing slug and said regent slug in said carrier stream.
8. A method according to claim 1 where the concentration of sample in said concentration gradients increases inward towards the central portion of said sample mixture slug.
9. A method according to claim 8 where the section of said sample mixture zone measured within said measuring cell is selected from the forward or rearward ends of said concentration gradient and not from said central portion.
10. A method according to claim 1 wherein reaction speeds at different sample concentrations within said sample zone are measured by changing the time period between introduction of said sample into said carrier stream and stopping said carrier stream flow.
11. In a method of analysis where a sample is introduced into a flowing carrier stream to form a sample mixture slug having a forward head portion, a rearward tail portion and a central portion, said sample dispersing to form reproducable concentration gradients in said head and tail portions in which the concentration of said sample varies, said sample undergoing a reaction while in said carrier stream, wherein the improvement comprises measuring the reaction speed of said sample at one or more selected sample concentrations within said concentration gradients by stopping the flow of said carrier stream and measuring the reaction of said sample at said selected sample concentrations for a period of time.
12. A method according to claim 11 in which measureable reaction products are produced by said sample reaction, said reaction product formation being related to said sample concentration, wherein said selected sample concentrations are determined indirectly by measurement of said reaction product formation.
13. A method of determining the change in a changing characteristic of a sample at selected sample concentrations comprising the steps of:
introducing a sample into a flowing carrier stream to form a sample mixture slug having a forward head portion, a rearward tail portion and a central portion, said sample dispersing within said sample mixture slug to form reproduceable concentration gradients in said head and tail portions in which the concentration of said sample varies, said sample having a measureable changing characteristic;
flowing said carrier stream and sample mixture slug through a measuring cell without removing the head or tail portion from said sample mixture slug; stopping the flow of said carrier stream in response to a selected concentration of sample within one of said concentration gradients as said sample mixture slug passes through said measuring cell; and
measuring the changing characteristic of said sample at said selected concentration for a period of time whereby the change in said characteristic of said sample at said selected concentration may be determined.
14. A method according to claim 13 wherein said changing characteristic is a reaction between said sample and one or more reagents added to said sample.
15. A method according to claim 14 wherein said reaction produces a measurable reaction product, said selected sample concentration being determined by measuring said reaction product.
US06296256 1978-06-14 1981-08-26 Stop-flow analysis Expired - Lifetime US4399225A (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
SE7806853 1978-06-14
SE7806853 1978-06-14

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
US06048002 Continuation 1979-06-13

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US06499199 Division US4504443A (en) 1978-06-14 1983-05-31 Stop-flow analysis

Publications (1)

Publication Number Publication Date
US4399225A true US4399225A (en) 1983-08-16

Family

ID=20335201

Family Applications (2)

Application Number Title Priority Date Filing Date
US06296256 Expired - Lifetime US4399225A (en) 1978-06-14 1981-08-26 Stop-flow analysis
US06499199 Expired - Lifetime US4504443A (en) 1978-06-14 1983-05-31 Stop-flow analysis

Family Applications After (1)

Application Number Title Priority Date Filing Date
US06499199 Expired - Lifetime US4504443A (en) 1978-06-14 1983-05-31 Stop-flow analysis

Country Status (5)

Country Link
US (2) US4399225A (en)
JP (1) JPH0220947B2 (en)
DE (1) DE2923970C2 (en)
FR (1) FR2432173B1 (en)
GB (1) GB2023286B (en)

Cited By (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4798803A (en) * 1985-07-10 1989-01-17 The Dow Chemical Company Method for titration flow injection analysis
US4958295A (en) * 1986-05-21 1990-09-18 Hercules Incorporated Analyzing apparatus and method for analysis of liquid samples
US4974592A (en) * 1988-11-14 1990-12-04 American Sensor Systems Corporation Continuous on-line blood monitoring system
US5001070A (en) * 1986-10-03 1991-03-19 Kone Oy Method for determining the total carbonate content of a fluid
US5019515A (en) * 1986-04-18 1991-05-28 Ciba-Geigy Corporation Method of controlling and optimizing industrial processes for the manufacture of textile finishing and improving agents via flow injection analysis
US5047351A (en) * 1986-09-01 1991-09-10 Fuji Photo Film Co., Ltd. Optical end-point type analytical method
US5055409A (en) * 1981-05-26 1991-10-08 Bifok Ab Method for reducing interferences in the analysis of substances which form volatile hydrides
US5284773A (en) * 1992-08-28 1994-02-08 The Uab Research Foundation Determination of lipoprotein concentration in blood by controlled dispersion flow analysis
WO1997047975A1 (en) * 1996-06-07 1997-12-18 Danfoss A/S Analysis apparatus and analysis method
US5845034A (en) * 1996-07-22 1998-12-01 Dsm Nv Radiation-curable, optical glass fiber coating composition and optical glass fiber drawing method
WO1999051980A2 (en) * 1998-04-03 1999-10-14 Symyx Technologies Rapid characterization of polymers
US6136197A (en) * 1998-05-27 2000-10-24 Battelle Memorial Institute Systems for column-based separations, methods of forming packed columns, and methods of purifying sample components
US6153154A (en) * 1998-05-27 2000-11-28 Battelle Memorial Institute Method for sequential injection of liquid samples for radioisotope separations
US6315952B1 (en) 1998-10-05 2001-11-13 The University Of New Mexico Plug flow cytometry for high throughput screening and drug discovery
US20020170365A1 (en) * 1999-09-30 2002-11-21 Sklar Larry A. Flow cytometry for high throughput screening
EP1308723A2 (en) * 1998-04-03 2003-05-07 Symyx Technologies, Inc. Rapid characterization of polymers by use of variable flow and light scattering
US6577392B1 (en) 1998-04-03 2003-06-10 Symyx Technologies, Inc. Characterization of non-biological polymers using flow-injection analysis with light-scattering detection
US20030148342A1 (en) * 2001-11-02 2003-08-07 Gau Vincent Jen-Jr System for detection of a component in a liquid
US6632619B1 (en) 1997-05-16 2003-10-14 The Governors Of The University Of Alberta Microfluidic system and methods of use
US20030207338A1 (en) * 1999-09-30 2003-11-06 Sklar Larry A. Wavy interface mixer
US6900021B1 (en) 1997-05-16 2005-05-31 The University Of Alberta Microfluidic system and methods of use
FR2864246A1 (en) * 2003-12-17 2005-06-24 Commissariat Energie Atomique Analyzing sample of liquid comprises injecting it into reaction loop coupled to means of lighting and means of detection
US20060054543A1 (en) * 2004-09-03 2006-03-16 Symyx Technologies, Inc. System and method for rapid chromatography with fluid temperature and mobile phase composition control
US20080105029A1 (en) * 2003-04-26 2008-05-08 Kanesho Soil Treatment Bvba Method and Device for Detecting Volatile Analytes in Air Samples
US7476360B2 (en) 2003-12-09 2009-01-13 Genefluidics, Inc. Cartridge for use with electrochemical sensor
US20120028364A1 (en) * 2010-08-02 2012-02-02 Ecolab Usa Inc. Stop-Flow Analytical Systems and Methods
US8823943B2 (en) 2009-05-21 2014-09-02 Intellicyt Corporation System and method for separating samples in a continuous flow
US9752964B1 (en) 2009-06-22 2017-09-05 Stc.Unm Flow cytometry apparatus pulling sample stream through observation chamber

Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4315754A (en) * 1979-08-28 1982-02-16 Bifok Ab Flow injection analysis with intermittent flow
JPS5847261A (en) * 1981-09-08 1983-03-18 Vickers Ltd Method and device for analyzing liquid sample
US4486097A (en) * 1981-09-09 1984-12-04 E. I. Du Pont De Nemours & Company, Inc. Flow analysis
US4610544A (en) * 1981-09-09 1986-09-09 Clifford Riley Flow analysis
JPH0432345B2 (en) * 1981-11-20 1992-05-29
DK160268C (en) * 1981-11-20 1991-07-22 Bifok Ab Mechanism for introducing sample solution to an analyzing apparatus for usegmenteret vaeskegennemstroemningsanalyse as well as procedures to inject into test solution to the analytical instruments
JPH0544623B2 (en) * 1983-08-30 1993-07-06 Nippon Bunko Kk
DE3688297D1 (en) * 1985-01-31 1993-05-27 Bifok Ab A method for non-segmented flow analysis using the interaction of radiation with a mounted in a flow cell solid material.
GB8600679D0 (en) * 1986-01-13 1986-02-19 Imp Group Plc Chemical analysis of tobacco/smoking-related products
US4859422A (en) * 1987-07-17 1989-08-22 Fisher Scientific Company Analysis system
DE3908040C2 (en) * 1989-03-13 1992-07-30 Kernforschungszentrum Karlsruhe Gmbh, 7500 Karlsruhe, De
EP0405583A1 (en) * 1989-06-30 1991-01-02 Kanzaki Paper Manufacturing Co., Ltd. Method and apparatus for flow analysis with enzyme electrode
DE4007246C2 (en) * 1990-03-08 1994-06-01 Forschungszentrum Juelich Gmbh Flow analysis method and apparatus
DE4018928C2 (en) * 1990-06-13 1996-03-28 Bodenseewerk Perkin Elmer Co Means for inputting of liquid samples in a carrier liquid flow
US5221521A (en) * 1990-07-26 1993-06-22 Kanzaki Paper Mfg. Co., Ltd. Sample liquid dilution system for analytical measurements
US5238853A (en) * 1990-09-14 1993-08-24 Instrumentation Laboratory S.R.L. Process and apparatus for the electrochemical determination of oxygen in a blood gas analyzer
DE4411269C2 (en) * 1994-03-31 1997-12-11 Danfoss As Apparatus and method for injecting a sample into a sample channel
DK174082B1 (en) * 1997-07-04 2002-05-27 Foss Electric As A method for determining the content of a component in a liquid sample
US8143070B2 (en) 2007-06-05 2012-03-27 Ecolab Usa Inc. Optical cell

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3690833A (en) * 1970-05-04 1972-09-12 Damon Corp Automated fluids analyzer having selectively interrupted flow
US3915644A (en) * 1973-03-27 1975-10-28 Cenco Medical Ind Inc Method and apparatus for determining concentrations by the analysis of reaction rates in continuously and discontinuously flowing samples
US4022575A (en) * 1974-09-16 1977-05-10 Block Engineering, Inc. Automatic chemical analyzer
US4224033A (en) * 1977-02-16 1980-09-23 Bifok Ab Programmable, continuous flow analyzer
US4315754A (en) * 1979-08-28 1982-02-16 Bifok Ab Flow injection analysis with intermittent flow

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2923970A (en) * 1960-02-09 genovese
CA1174833A (en) * 1980-06-10 1984-09-25 Alan Queen Stopped-flow apparatus

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3690833A (en) * 1970-05-04 1972-09-12 Damon Corp Automated fluids analyzer having selectively interrupted flow
US3915644A (en) * 1973-03-27 1975-10-28 Cenco Medical Ind Inc Method and apparatus for determining concentrations by the analysis of reaction rates in continuously and discontinuously flowing samples
US4022575A (en) * 1974-09-16 1977-05-10 Block Engineering, Inc. Automatic chemical analyzer
US4224033A (en) * 1977-02-16 1980-09-23 Bifok Ab Programmable, continuous flow analyzer
US4315754A (en) * 1979-08-28 1982-02-16 Bifok Ab Flow injection analysis with intermittent flow

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Hansen et al., "Flow Injection Analysis, etc.," Analytica Chimica Acta, 89(1977), pp. 241-254. *

Cited By (50)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5055409A (en) * 1981-05-26 1991-10-08 Bifok Ab Method for reducing interferences in the analysis of substances which form volatile hydrides
US4798803A (en) * 1985-07-10 1989-01-17 The Dow Chemical Company Method for titration flow injection analysis
US5019515A (en) * 1986-04-18 1991-05-28 Ciba-Geigy Corporation Method of controlling and optimizing industrial processes for the manufacture of textile finishing and improving agents via flow injection analysis
US4958295A (en) * 1986-05-21 1990-09-18 Hercules Incorporated Analyzing apparatus and method for analysis of liquid samples
US5047351A (en) * 1986-09-01 1991-09-10 Fuji Photo Film Co., Ltd. Optical end-point type analytical method
US5001070A (en) * 1986-10-03 1991-03-19 Kone Oy Method for determining the total carbonate content of a fluid
US4974592A (en) * 1988-11-14 1990-12-04 American Sensor Systems Corporation Continuous on-line blood monitoring system
US5284773A (en) * 1992-08-28 1994-02-08 The Uab Research Foundation Determination of lipoprotein concentration in blood by controlled dispersion flow analysis
WO1997047975A1 (en) * 1996-06-07 1997-12-18 Danfoss A/S Analysis apparatus and analysis method
US5845034A (en) * 1996-07-22 1998-12-01 Dsm Nv Radiation-curable, optical glass fiber coating composition and optical glass fiber drawing method
US6632619B1 (en) 1997-05-16 2003-10-14 The Governors Of The University Of Alberta Microfluidic system and methods of use
US20040178071A1 (en) * 1997-05-16 2004-09-16 The Governors Of The University Of Alberta Microfluidic system and methods of use
US6900021B1 (en) 1997-05-16 2005-05-31 The University Of Alberta Microfluidic system and methods of use
EP1308723A3 (en) * 1998-04-03 2004-08-11 Symyx Technologies, Inc. Rapid characterization of polymers by use of variable flow and light scattering
WO1999051980A3 (en) * 1998-04-03 2001-03-22 Symyx Technologies Inc Rapid characterization of polymers
EP1308723A2 (en) * 1998-04-03 2003-05-07 Symyx Technologies, Inc. Rapid characterization of polymers by use of variable flow and light scattering
US6577392B1 (en) 1998-04-03 2003-06-10 Symyx Technologies, Inc. Characterization of non-biological polymers using flow-injection analysis with light-scattering detection
WO1999051980A2 (en) * 1998-04-03 1999-10-14 Symyx Technologies Rapid characterization of polymers
US6136197A (en) * 1998-05-27 2000-10-24 Battelle Memorial Institute Systems for column-based separations, methods of forming packed columns, and methods of purifying sample components
US6153154A (en) * 1998-05-27 2000-11-28 Battelle Memorial Institute Method for sequential injection of liquid samples for radioisotope separations
US6315952B1 (en) 1998-10-05 2001-11-13 The University Of New Mexico Plug flow cytometry for high throughput screening and drug discovery
US7842244B2 (en) 1999-09-30 2010-11-30 Stc.Unm Flow cytometry for high throughput screening
US20030207338A1 (en) * 1999-09-30 2003-11-06 Sklar Larry A. Wavy interface mixer
US6878556B2 (en) 1999-09-30 2005-04-12 Science & Technology Corporation @ Unm Flow cytometry for high throughput screening
US6890487B1 (en) 1999-09-30 2005-05-10 Science & Technology Corporation ©UNM Flow cytometry for high throughput screening
US9677989B2 (en) 1999-09-30 2017-06-13 Stc.Unm Flow cytometry for high throughput screening
US9267892B2 (en) 1999-09-30 2016-02-23 Stc.Unm Flow cytometry for high throughput screening
US8637261B2 (en) 1999-09-30 2014-01-28 Stc.Unm Flow cytometry for high throughput screening
US20050180887A1 (en) * 1999-09-30 2005-08-18 Science & Technology Corporation @ Unm Flow cytometry for high throughput screening
US8268571B2 (en) 1999-09-30 2012-09-18 Stc.Unm Flow cytometry for high throughput screening
US8021872B2 (en) 1999-09-30 2011-09-20 Stc.Unm Flow cytometry for high throughput screening
US20020170365A1 (en) * 1999-09-30 2002-11-21 Sklar Larry A. Flow cytometry for high throughput screening
US20110045995A1 (en) * 1999-09-30 2011-02-24 Stc.Unm Flow cytometry for high thorughput screening
US7416903B2 (en) 1999-09-30 2008-08-26 Stc.Unm Wavy interface mixer
US20080292500A1 (en) * 1999-09-30 2008-11-27 Stc.Unm Flow cytometry for high throughput screening
US7368084B2 (en) 1999-09-30 2008-05-06 Stc.Unm Flow cytometry for high throughput screening
US20030148342A1 (en) * 2001-11-02 2003-08-07 Gau Vincent Jen-Jr System for detection of a component in a liquid
US7767437B2 (en) * 2001-11-02 2010-08-03 Genefluidics, Inc. System for detection of a component in a liquid
US20080105029A1 (en) * 2003-04-26 2008-05-08 Kanesho Soil Treatment Bvba Method and Device for Detecting Volatile Analytes in Air Samples
US7950270B2 (en) * 2003-04-26 2011-05-31 Reiner Kober Method and device for detecting volatile analytes in air samples
US7476360B2 (en) 2003-12-09 2009-01-13 Genefluidics, Inc. Cartridge for use with electrochemical sensor
WO2005059519A1 (en) * 2003-12-17 2005-06-30 Commissariat A L'energie Atomique Method and system for analysing a liquid sample
US20060210961A1 (en) * 2003-12-17 2006-09-21 Alastair Magnaldo Method and system for analysing a liquid sample
FR2864246A1 (en) * 2003-12-17 2005-06-24 Commissariat Energie Atomique Analyzing sample of liquid comprises injecting it into reaction loop coupled to means of lighting and means of detection
US20060054543A1 (en) * 2004-09-03 2006-03-16 Symyx Technologies, Inc. System and method for rapid chromatography with fluid temperature and mobile phase composition control
US7507337B2 (en) 2004-09-03 2009-03-24 Symyx Technologies, Inc. System and method for rapid chromatography with fluid temperature and mobile phase composition control
US8823943B2 (en) 2009-05-21 2014-09-02 Intellicyt Corporation System and method for separating samples in a continuous flow
US9752964B1 (en) 2009-06-22 2017-09-05 Stc.Unm Flow cytometry apparatus pulling sample stream through observation chamber
US8748191B2 (en) * 2010-08-02 2014-06-10 Ecolab Usa Inc. Stop-flow analytical systems and methods
US20120028364A1 (en) * 2010-08-02 2012-02-02 Ecolab Usa Inc. Stop-Flow Analytical Systems and Methods

Also Published As

Publication number Publication date Type
DE2923970A1 (en) 1980-01-03 application
FR2432173B1 (en) 1984-11-16 grant
FR2432173A1 (en) 1980-02-22 application
GB2023286B (en) 1983-02-09 grant
GB2023286A (en) 1979-12-28 application
JPH0220947B2 (en) 1990-05-11 grant
JPS5529791A (en) 1980-03-03 application
US4504443A (en) 1985-03-12 grant
DE2923970C2 (en) 1987-09-03 grant

Similar Documents

Publication Publication Date Title
Cashel The control of ribonucleic acid synthesis in Escherichia coli IV. Relevance of unusual phosphorylated compounds from amino acid-starved stringent strains
Bode et al. Spontaneous decay of oxidized ascorbic acid (dehydro-L-ascorbic acid) evaluated by high-pressure liquid chromatography.
Schügerl Progress in monitoring, modeling and control of bioprocesses during the last 20 years
Guilbault et al. Fluorometric Procedure for Measuring the Activity of Dehydrogenases.
Pitot et al. The automated assay of complete enzyme reaction rates: I. Methods and results
Carey et al. Selection of adsorbates for chemical sensor arrays by pattern recognition
Růžička et al. Optosensing at active surfaces—A new detection principle in flow injection analysis
US4759828A (en) Glucose electrode and method of determining glucose
Guilbault Use of enzymes in analytical chemistry
Trojanowicz Flow injection analysis
Eisenthal et al. Enzyme assays: a practical approach
Seitz et al. Chemiluminescence and bioluminescence analysis: fundamentals and biomedical applications
Tiffany et al. Enzymatic kinetic rate and end-point analyses of substrate, by use of a GeMSAEC fast analyzer
Neeley Simple automated determination of serum or plasma glucose by a hexokinase/glucose-6-phosphate dehydrogenase method
Baykov et al. A simple and sensitive apparatus for continuous monitoring of orthophosphate in the presence of acid-labile compounds
Foster et al. Stable reagents for determination of serum triglycerides by a colorimetric Hantzsch condensation method
US4490234A (en) Method for measuring ionic concentration utilizing an ion-sensing electrode
Pardue A comprehensive classification of kinetic methods of analysis used in clinical chemistry.
US4425427A (en) Simultaneous, kinetic, spectrophotometric analysis of blood serum for multiple components
US3838011A (en) Process and apparatus for the quantitative determination of an enzymatically reactive substance
Anderson et al. Liquid chromatographic-fluorometric system for the determination of indoles in physiological samples
Grayeski Chemiluminescence analysis
Grau et al. Recent methodological advances in the analysis of nitrite in the human circulation: nitrite as a biochemical parameter of the L-arginine/NO pathway
US5223224A (en) Sensor arrangement for flow injection analysis
Riggin et al. Determination of acetaminophen in pharmaceutical preparations and body fluids by high‐performance liquid chromatography with electrochemical detection

Legal Events

Date Code Title Description
FPAY Fee payment

Year of fee payment: 4

FPAY Fee payment

Year of fee payment: 8

REMI Maintenance fee reminder mailed
SULP Surcharge for late payment
FPAY Fee payment

Year of fee payment: 12